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Clinical record

On arrival at the hospital his capillary blood glucose level was 4.3 mmol/L. He was speaking Indonesian and was alert and cooperative. He reported having diet-controlled non-insulin-dependent (type 2) diabetes mellitus, ischaemic heart disease (with coronary artery bypass surgery 12 years previously), hypertension and hypercholesterolaemia. He was taking amlodipine, aspirin and atorvastatin, but denied taking any medications for his diabetes. He was given some sandwiches while the history was being taken and an examination was performed.

At 2:45 pm his capillary blood glucose level was found to be 2.1 mmol/L. Shortly after this, the laboratory rang to give a formal venous glucose concentration result of 2.9 mmol/L for a sample taken at 1:48 pm. Despite being given sugary drinks, then increasing dextrose infusions and intermittent boluses of dextrose, each time his blood sugar was retested it was found to be low (see Box). A 50 mL per hour infusion of 50% dextrose was required to prevent hypoglycaemia.

After the first bolus of 50% dextrose it was discovered that he could speak English fluently. He confirmed his diabetes was diet-controlled and that he was not taking any hypoglycaemic medications. The lack of any obvious cause for the hypoglycaemia prompted us to consider rarer causes, and, in response to direct questioning about herbal and traditional medication, he admitted to taking a preparation called "ZhenQi" for his diabetes, which he had purchased in Malaysia. He had been taking this medication for the last five years, initially taking five capsules per day, then having increased the dose to three capsules three times daily (with no dose alteration) for the last two years. The label on the bottle of this preparation listed the ingredients as ginseng, pearl, ram's horn, bark and "frog extract". He had started a new bottle of the preparation recently, coinciding with the onset of the "flu"-like symptoms (lethargy, feeling cold and tremor). Serum taken during the period of hypoglycaemia (when his glucose level was 2.9 mmol/L) had elevated levels of C-peptide (3.80 nmol/L; normal range, 0.20-0.90 nmol/L) and insulin (50 mU/L; normal range, 3-26 mU/L). Analysis of the herbal medication capsules by gas chromatography and mass spectrometry (by PathCentre, Perth, Western Australia) revealed the presence of glibenclamide.

Infusions of 50% dextrose and potassium were required for 20 hours, then reduced gradually over the next 24 hours. The serum insulin level had returned to normal 36 hours after admission. He was discharged on Day 3.

Discussion

The diagnosis of hypoglycaemia rests on three criteria (Whipple's triad) of plasma hypoglycaemia, symptoms attributable to a low blood sugar level and resolution of symptoms with correction of the hypoglycaemia.³ There are many causes of hypoglycaemia,^2-4 but it is most commonly the result of an excess of either insulin or oral hypoglycaemic medications combined with reduced sugar intake or increased activity.²

Our patient's initial claims that he was not taking any medications for glycaemic control led to a search for other causes. Although he had been taking the same dose of the herbal preparation for two years, we felt that it was the most likely cause of the hypoglycaemia. Insulin and C-peptide levels were therefore measured and both were elevated, indicating an endogenous insulin source as the cause. This can result from either an insulinoma, sulfonylurea drug (which stimulates the pancreatic islet cells to release insulin), drugs with a sulfonylurea-like action (eg, quinine)⁴ or autoimmune hypoglycaemia. Insulinomas usually cause semiautonomous release of insulin, resulting in fasting hypoglycaemia. In response to meals these tumours usually respond subnormally, so that postprandial glucose levels are normal or even mildly elevated,² although postprandial hypoglycaemia can occur. This patient's persistent hypoglycaemia despite food would therefore be atypical for an insulinoma. However, computed tomography (CT) of the abdomen was performed (prior to the insulin and C-peptide levels being available) to exclude this possibility, or that of a large sarcoma (which can cause hypoglycaemia because of insulin-like growth-factor II release) — no pancreatic or intra-abdominal masses were detected. Insulinomas may be too small to be seen on CT scans⁵ and further investigation with endoscopic ultrasound was considered, if no other cause for the hypoglycaemia became apparent.

Sulfonylurea overdose can lead to profound hypoglycaemia, with chlorpropamide and glibenclamide being the agents most frequently implicated.⁶ Both prolonged and recurrent hypoglycaemia must be expected. Potassium supplementation is often required. Dextrose infusions are usually sufficient, but can stimulate further insulin release from the sulfonylurea-primed beta cells. Octreotide and diazoxide both inhibit insulin release and have been recommended for treating severe poisoning refractory to dextrose.^7,8 Steroids and glucagon have also been recommended, but are thought to be less effective.⁸ In our patient, analysis of the herbal medication capsules revealed the presence of glibenclamide. Plasma tests to screen for sulfonylureas are available and can be used to detect inadvertent or surreptitious ingestion.⁹

The use of herbal and alternative medicine is becoming more common, and it has been estimated that almost half of the Australian population use some form of such products within a 12-month period.¹ Many patients do not inform their doctors that they take them.¹⁰ It is therefore important to ask directly whether patients are taking such substances. Numerous herbal preparations have been shown to affect blood glucose levels through various mechanisms, although they are usually limited by toxicity or relative lack of efficacy compared with standard medications.^11,12 The lack of standardisation of ingredients and preparation also causes problems.¹³ Contamination with "conventional" medications has been reported to cause adverse effects.^14,15 In this case, we felt it most likely that the sulfonylurea had been added to the herbal ingredients in the preparation of the capsules.

Conclusion

Competing interests: None.  

References

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11. Bailey CJ, Day C. Traditional plant medicines as treatments for diabetes. Diabetes Care 1989; 12: 553-563.
12. Miller LG. Herbal medicinals. Arch Intern Med 1998; 158: 2200-2211.
13. Shaw D, Leon C, Kolev S, Murray V. Traditional remedies and food supplements. Drug Safety 1997; 17: 342-356.
14. Rios CA, Sahud MA. Agranulocytosis caused by Chinese herbal medicines. Dangers of medications containing aminopyrine and phenylbutazone. JAMA 1975; 231: 352-355.
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Authors' details

Reprints will not be available from the authors.
Correspondence: Dr A M Goudie, Royal Perth Hospital, Box X2213, GPO, Perth, WA 6847.
adriangoudieATyahoo.com.au

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